A Simulation Study of Diffusion-convection Interaction and Its Effect on Multiple Breath Washout Indices

Experimental studies of acinar ventilation heterogeneity (S) derived from the multiple breath washout have shown the potential of S to pick up structural change in lung disease. Recent S data suggest that even when intra-acinar structure is unaltered, the combination of convection, diffusion and number of acini fed by patent terminal bronchioles can modify S. We show here how S is affected by structural features such as the secondary alveolar septa, intra-acinar ramification and number of ventilated acini. The simulations also predict relationships between respective alterations in S and washout indices such as lung clearance index (LCI) and alveolar mixing efficiency (AME). This was verified experimentally, with highly significant correlations between S and LCI (r = +0.85;p < 0.001) and between S and AME (r = - 0.92; p < 0.001). We have shown how acinar ventilation heterogeneity can be affected by a reduction of number of ventilated acini, a change in overall alveolization or in intra-acinar alveolization pattern, via their impact on the balance between convection and diffusion at acinar level.